IBT-V02: A Multicomponent Toxoid Vaccine Protects Against Primary and Secondary Skin Infections Caused by Staphylococcus aureus

Abstract

Staphylococcus aureus causes a wide range of diseases from skin infections to life threatening invasive diseases such as bacteremia, endocarditis, pneumonia, surgical site infections, and osteomyelitis. Skin infections such as furuncles, carbuncles, folliculitis, erysipelas, and cellulitis constitute a large majority of infections caused by S. aureus (SA). These infections cause significant morbidity, healthcare costs, and represent a breeding ground for antimicrobial resistance. Furthermore, skin infection with SA is a major risk factor for invasive disease. Here we describe the pre-clinical efficacy of a multicomponent toxoid vaccine (IBT-V02) for prevention of S. aureus acute skin infections and recurrence. IBT-V02 targets six SA toxins including the pore-forming toxins alpha hemolysin (Hla), Panton-Valentine leukocidin (PVL), leukocidin AB (LukAB), and the superantigens toxic shock syndrome toxin-1 and staphylococcal enterotoxins A and B. Immunization of mice and rabbits with IBT-V02 generated antibodies with strong neutralizing activity against toxins included in the vaccine, as well as cross-neutralizing activity against multiple related toxins, and protected against skin infections by several clinically relevant SA strains of USA100, USA300, and USA1000 clones. Efficacy of the vaccine was also shown in non-naïve mice pre-exposed to S. aureus. Furthermore, vaccination with IBT-V02 not only protected mice from a primary infection but also demonstrated lasting efficacy against a secondary infection, while prior challenge with the bacteria alone was unable to protect against recurrence. Serum transfer studies in a primary infection model showed that antibodies are primarily responsible for the protective response.

Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches

“…Integrated Bio Therapeutics has developed a heptavalent S. aureus vaccine consisting of seven S. aureus toxoids: Hla, Panton–Valentine Leukocidin (PVL) F and S subunits, Leukocidin A/B, SEA, SEB, and Toxic shock syndrome toxin 1. Preclinical data have shown that this vaccine, named IBT-V02, confers protection to both mice and rabbits against S. aureus skin infection, with protection being entirely mediated by vaccine-induced antibodies [ 53 ].…”

Staphylococcus aureus Toxins: An Update on Their Pathogenic Properties and Potential Treatments

“…IBT-VO2 is a multivalent vaccine currently under investigation. α-hemolysin, PVL LukS, LukF, LukAB, enterotoxins A and B, and toxic shock syndrome toxin 1 toxoids are all included in this heptavalent vaccine [167]. The multi-subunit vaccine generates an antibody response that is cross-reactive with 12 to 15 S. aureus toxins and gives protection in different mice and rabbit infection models due to structural similarities [167].…”

“…α-hemolysin, PVL LukS, LukF, LukAB, enterotoxins A and B, and toxic shock syndrome toxin 1 toxoids are all included in this heptavalent vaccine [167]. The multi-subunit vaccine generates an antibody response that is cross-reactive with 12 to 15 S. aureus toxins and gives protection in different mice and rabbit infection models due to structural similarities [167]. Recently, IBT-VO2 entered a Phase I clinical study after completing the encouraging pre-clinical phase, and as a result, received additional funding to help it progress.…”

Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies

“…Integrated BioTherapeutics have developed a heptavalent S. aureus vaccine consisting of seven S. aureus toxoids: Hla, Panton-Valentine Leukocidin (PVL) F and S subunits, Leukocidin A/B, SEA, SEB and Toxic shock syndrome toxin 1 ( 157 ). Preclinical data has shown that this vaccine, named IBT-V02, confers protection to both mice and rabbits against S. aureus skin infection, with protection being entirely mediated by vaccine-induced antibodies ( 142 ). Interestingly, vaccine efficacy (as measured through the development of infection-induced skin lesions) was unaffected when mice were pre-exposed intradermally to a low dose of S. aureus prior to vaccination.…”